Admp regulates tail bending by controlling the intercalation of the ventral epidermis through myosin phosphorylation

Chordate tailbud embryos have similar morphological features, including a bending tail. A recent study revealed that the actomyosin of the notochord changes the contractility and drive tail bending of the early Ciona tailbud embryo. Yet, the upstream regulator of tail bending remains unknown. In this study, we find that Admp regulates tail bending of Ciona mid-tailbud embryos. Anti-pSmad antibody signal was detected at the ventral midline tail epidermis. Admp knock-down embryo completely inhibited the ventral tail bending and reduced the number of the triangular-shaped cells, which has the apical accumulation of the myosin phosphorylation and inhibited specifically the cell-cell intercalation of the ventral epidermis. The degree of myosin phosphorylation of the ventral cells and tail bending were correlated. Finally, the laser cutter experiments demonstrated the myosin-phosphorylation-dependent tension of the ventral midline epidermis during tail bending. We conclude that Admp is an upstream regulator of the tail bending by controlling myosin phosphorylation and its localization of ventral epidermal cells. These data reveal a new aspect of the function of the Admp that might be evolutionarily conserved in bilaterian animals.Summary StatementAdmp is an upstream regulator of the bending of the tail in the tailbud embryo regulating tissue polarity of the ventral midline epidermis by phosphorylation of myosin.

Coordination of biradial-to-radial symmetry and tissue polarity by HD-ZIP II proteins

Symmetry establishment is a critical process in the development of multicellular organs and requires careful coordination of polarity axes while cells actively divide within tissues. Formation of the apical style in the Arabidopsis gynoecium involves a bilateral-to-radial symmetry transition, a stepwise process underpinned by the dynamic distribution of the plant morphogen auxin. Here we show that SPATULA (SPT) and the HECATE (HEC) bHLH proteins mediate the final step in the style radialisation process and synergistically control the expression of adaxial-identity genes, HOMEOBOX ARABIDOPSIS THALIANA 3 (HAT3) and ARABIDOPSIS THALIANA HOMEOBOX 4 (ATHB4). HAT3/ATHB4 module drives radialisation of the apical style by promoting basal-to-apical auxin flow and via a negative feedback mechanism that finetune auxin distribution through repression of SPT expression and cytokinin sensitivity. Thus, this work reveals the molecular basis of axes-coordination and hormonal cross-talk during the sequential steps of symmetry transition in the Arabidopsis style.

Intercellular and intracellular cilia orientation is coordinated by CELSR1 and CAMSAP3 in oviduct multi-ciliated cells

ABSTRACTThe molecular mechanisms by which cilia orientation is coordinated within and between multi-ciliated cells (MCCs) are not fully understood. In the mouse oviduct, MCCs exhibit a characteristic basal body (BB) orientation and microtubule gradient along the tissue axis. The intracellular polarities were moderately maintained in cells lacking CELSR1 (cadherin EGF LAG seven-pass G-type receptor 1), a planar cell polarity (PCP) factor involved in tissue polarity regulation, although the intercellular coordination of the polarities was disrupted. However, CAMSAP3 (calmodulin-regulated spectrin-associated protein 3), a microtubule minus-end regulator, was found to be critical for determining the intracellular BB orientation. CAMSAP3 localized to the base of cilia in a polarized manner, and its mutation led to the disruption of intracellular coordination of BB orientation, as well as the assembly of microtubules interconnecting BBs, without affecting PCP factor localization. Thus, both CELSR1 and CAMSAP3 are responsible for BB orientation but in distinct ways; their cooperation should therefore be critical for generating functional multi-ciliated tissues.

Celsr1 and CAMSAP3 differently regulate intercellular and intracellular cilia orientation in oviduct multiciliated cells

SummaryThe molecular mechanisms by which cilia orientation is coordinated within and between multiciliated cells (MCCs) is not fully understood. By observing the orientation of basal bodies (BB) in MCCs of mouse oviducts, here, we show that Celsr1, a planar cell polarity (PCP) factor involved in tissue polarity regulation, is dispensable for determining BB orientation in individual cells, whereas CAMSAP3, a microtubule minus-end regulator, is critical for this process but not for PCP. MCCs exhibit a characteristic BB orientation and microtubule gradient along the tissue axis, and these intracellular polarities were maintained in the cells lacking Celsr1, although the intercellular coordination of the polarities was partly disrupted. On the other hand, CAMSAP3 regulated the assembly of microtubules interconnecting BBs by localizing at the BBs, and its mutation led to disruption of intracellular coordination of BB orientation, but not affecting PCP factor localization. Thus, both Celsr1 and CAMSAP3 are responsible for BB orientation but in distinct ways; and therefore, their cooperation should be critical for generating functional multiciliated tissues.

Occludin protects secretory cells from ER stress by facilitating SNARE-dependent apical protein exocytosis

Tight junctions (TJs) are fundamental features of both epithelium and endothelium and are indispensable for vertebrate organ formation and homeostasis. However, mice lackingOccludin(Ocln) develop relatively normally to term. Here we show thatOclnis essential for mammary gland physiology, as mutant mice fail to produce milk. Surprisingly,Oclnnull mammary glands showed intact TJ function and normal epithelial morphogenesis, cell differentiation, and tissue polarity, suggesting thatOclnis not required for these processes. Using single-cell transcriptomics, we identified milk-producing cells (MPCs) and found they were progressively more prone to endoplasmic reticulum (ER) stress as protein production increased exponentially during late pregnancy and lactation. Importantly,Oclnloss in MPCs resulted in greatly heightened ER stress; this in turn led to increased apoptosis and acute shutdown of protein expression, ultimately leading to lactation failure in the mutant mice. We show that the increased ER stress was caused by a secretory failure of milk proteins inOclnnull cells. Consistent with an essential role in protein secretion, Occludin was seen to reside on secretory vesicles and to be bound to SNARE proteins. Taken together, our results demonstrate thatOclnprotects MPCs from ER stress by facilitating SNARE-dependent protein secretion and raise the possibility that other TJ components may participate in functions similar toOcln.

Nervous System and Tissue Polarity Dynamically Adapt to New Morphologies in Planaria

The coordination of tissue-level polarity with organism-level polarity is crucial in development, disease, and regeneration. Exploiting the flexibility of the body plan in regenerating planarians, we used mirror duplication of the primary axis to show how established tissue-level polarity adapts to new organism-level polarity. Tracking of cilia-driven flow to characterize planar cell polarity of the epithelium revealed a remarkable reorientation of tissue polarity in double-headed planarians. This reorientation is driven by signals produced by the intact brain and is not hampered by radiation-induced removal of stem cells. The nervous system itself adapts its polarity to match the new organismal anatomy in these animals as revealed by distinct regenerative outcomes driven by polarized nerve transport. Thus, signals from the central nervous system can dynamically control and re-orient tissue-level polarity to match the organism-level anatomical configuration, illustrating a novel role of the nervous system in the regulation of patterning.

ya||a: GPU-powered Spheroid Models for Mesenchyme and Epithelium

ya||a is yet another parallel agent-based model for morphogenesis. It is several orders of magnitude faster than onventional models, because it runs on GPUs and because it has been designed for performance: Previously only complex and therefore computationally expensive models could simulate both mesenchyme and epithelium. We chose o extend the simple spheroid model by the addition of spin-like polarities to simulate epithelial sheets and tissue polarity. We also incorporate recently developed models for protrusions and migration. ya||a is written in concise, plain UDA/C++ and available at github.com/germannp/yalla under the MIT license.